Low Vitamin D Linked to Alzheimer’s Disease

Written By: Pauline Anderson

Author: Pauline Anderson

September 28, 2012 — Yet another study has linked low vitamin D levels with significant health issues — in this case, poor cognition.

In this latest systematic review of the literature, people with Alzheimer’s disease (AD) had lower concentrations of vitamin D than those without AD, and better cognitive test results were linked to higher vitamin D concentrations.

Overall, the results provide sufficient evidence to warrant further investigation to determine whether a cause-and-effect relationship exists, said lead author Cynthia Balion, PhD, a clinical biochemist and associate professor, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

“I think we have really good data now to make it clear that people need to do the interventional studies and see whether or not giving vitamin D helps people at higher risk for developing cognitive decline,” Dr. Balion toldMedscape Medical News.

The new review was published in the September 25 issue of Neurology.


Comprehensive Analysis

Dr. Balion pointed out that some factors affecting vitamin D concentrations, including skin pigmentation, age, genetics, and time of sun exposure and testing, were not considered by some studies. As well, she said, reverse causation can’t be ruled out because older people may have poor nutrition and spend less time exposed to sunlight, a major source of vitamin D. Despite these limitations, “I’m pretty happy saying that vitamin D plays a role in brain health,” she said.

How exactly vitamin D protects the brain is not clear, but research suggests that vitamin D acts as a neurosteroid, said Dr. Balion. At the molecular level, the brain can synthesize the active form of vitamin D [1,25(OH)D] within several cell types and regions, predominantly in the hypothalamus and large neurons in the substantia nigra. Many genes are regulated by vitamin D, which contributes to neuroprotection by modulating the production of such things as nerve growth factor, and regulating neurotransmitters.

The ideal concentration of vitamin D is also not really known, said Dr. Balion. “We tried to assess that with the data that we had from all these papers, and some studies show there might be this magic cut point and other studies did not really find a cut point. Most studies aren’t designed to look for that because they’re not outcome studies.”

However, she noted that 2 cut points are recommended worldwide: 50 and 75 nmol/L. Canada, for example, recommends the upper level for bone health.

Physicians should recommend supplements for patients not getting sufficient vitamin D, said Dr. Balion. Many jurisdictions, including Canada, recommend 600 IU of vitamin D daily for older children and adults; recommendations differ for younger children and pregnant women.

Vitamin D Testing

Ontario’s universal healthcare system does not provide for vitamin D testing except for certain conditions (osteoporosis, osteopenia, rickets, malabsorption syndrome, renal disease, or taking medications that affect vitamin D metabolism) because the evidence is not yet established, said Dr. Balion.

The United States has recommendations similar to Canada’s, Dr. Shah notes. Americans are becoming more aware of vitamin D’s health benefits and are taking more supplements; however, although the vitamin is fat soluble, and so may be safer than some other vitamins when taken at higher doses, Dr. Shah noted that it can still lead to muscle pains and gastrointestinal tract problems.

When asked to comment on this review, Dr. Shah said, “it helps clinicians like me and researchers to understand where the state of science is in this field, and it tells us we have a lot more work to do.” He noted that of the 37 papers included in the review, only a few were clinical trials.

However, that may be changing. VITAL (VITamin D and OmegA-3 TriaL), a large 5-year clinical trial sponsored by the National Institutes of Health, is randomly assigning 20,000 people across the United States. The placebo-controlled trial will investigate whether vitamin D or omega fatty acid affects various aspects of health, including cognition.

Dr. Shah raised several important issues pertaining to the analysis. For one thing, results of vitamin D studies may depend on where participants live and the time of the year that testing was done.

He also noted that most studies were probably not done in diverse populations. “I suspect that subjects were mainly Caucasian,” but because the United States has an increasingly diverse population, “we need to have measures of these effects in various older adults.”

Dr. Shah said that as with any meta-analysis, some publication bias probably exists, with negative studies not being published or available for review.

He also questioned whether intervening through supplementation to arrive at a target vitamin D level would affect outcomes. He used the example of high-density lipoprotein, where experts believed that raising levels would reduce risks for heart disease. Preliminary research suggests that such efforts not only might not produce the expected result but also may cause some harm in terms of adverse effects.

The study was funded by the Ontario Research Coalition of Research Institutes/Centers on Health & Aging, Ontario Ministry of Long-Term Care. Dr. Balion receives research support from the Canadian Institutes of Health Research, the Agency for Healthcare Research and Quality, the Canada Foundation for Innovation (CFI), and the Ontario Ministry of Health and Long-Term Care. For disclosures for other authors, see original paper. Dr. Shah has disclosed no relevant financial relationships.

Neurology. 2012;79:1397-1405. Abstract

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